J . Org. C h e m . 1994,59,8307-8311
De Novo Approach to Dideoxyribosides. 5-Endo-trig-likeCyclizations of &Hydroxy Enol Ethers Bruce H. Lipshutz* and Raymond Tirado Department of Chemistry, University of California, S a n t a Barbara, California 93106 Received September 9,1994
Electrophile-initiated cyclizations of homoallylic alcohols which proceed via 5-endo-trig-likeclosures have been shown to afford substituted tetrahydrofurans, key subunits of polyether natural products, with considerable stereocontrol. Substrates bearing either (E)-or (Z)-alkyl or (heterolaryl-substitutedolefins, with occasional substitution at the allylic (3) position, readily react in the presence of reagents (E+)such as 12 (with or without MI) salts), PhSeC1, protons, and Hg(I1) salts (eq l).l Replacecan be reduced
1-
controlledtogive predominantly cis or trans
ment of the alkyVary1 group in the educt with an ether unit (OR) presents opportunities for cyclizations involving enol ethers 1,the result of which might lead to controlled access to (di)deoxyriboses 2 (eq 2h2 We now report on
the preparation of precursors 1,conditions that allow for their stereoselective cyclizations to 2, and a comparison of commonly employed electrophilic reagents, E+, in terms of the extent of stereoselectivity realized with each. From glycidol benzyl or thexyldimethylsilyl ether (3a, epoxide opening to 4 was readily 3b, re~pectively),~ achieved with an alanate reagent4s5derived from Me&l (1)For cyclizations using PhSeX, see: (a)Mihelich, E. D.; Hite, G. A. J.Am. Chem. SOC.1992,114,7318.(b) Lipshutz, B. H.; Barton, J. C. Zbid. 1992,114,1084.(c) Kang, S. H.; Hwang, T. S.; Kim, W. J.; Lim, J. K. Tetrahedron Lett. 1991,32,4015.(d) Kang, S.H. Ibid. 1990, 31,5917.(e) Mihelich, E. D.; Hite, G. A. J.Am. Chem. SOC.1990,112, 8995.(0 Murata, S.;Suzuki, T. Tetrahedron Lett. 1990,31,6535. Using iodine: (g) Kang, S. H.; Lee, S. B. Tetrahedron Lett. 1993,34,7579. (h) Kang, S.H.; Lee, S. B. Ibid. 1993,34,1955.(i)Bedford, S.B.; Bell, K. E.; Fenton, G.; Hayes, C. J.; Knight, D. W.; Shaw, D. Ibid. 1902, 33,6511.(j) Bennett, F.; Bedford, S. B.; Bell, K. E.; Fenton, G.; Knight, D. W.; Shaw, D. Zbid. 1992,33,6507.(k) Marek, I.; Lefrancois, J.-M.; Normant, J.-F. Zbid. 1992,33, 1747.(1) Evans, R. D.; Magee, J. W.; Herman Shauble, J. Synthesis 1988,862.For cyclizations using other sources of electrophiles, see, for example: (m) Kocovsky, P.; Pour, M. J. Org. Chem. 1990,55,5580. (n) Craig, D.; Smith, A. M. Tetrahedron Lett. 1992,33,695.(0)Polt, R.; Wijayaratne, T. Zbid. 1991,32,4831. (2)For the synthesis of carbohydrates, in particular from noncarbohydrate precursors, see: (a) Mash, E. A.; Arterburn, J. B.; Fryling, J. A.; Mitchell, S. H. J. Org. Chem. 1991,56, 1088.(b) Mash, E. A. Synlett 1991,529.(c) Ager, D. J.; East, M. B. Tetrahedron 1993,49, 5683.
8307
and the lithiated form of an acetylenic ether.6 Reduction with LAH in THF afforded the (E)-isomers 5, while hydrogenation over Lindlar catalyst led to (Z)-enolethers 6 (Scheme 1). Cyclizations of various substrates were examined, induced by PhSeCl or Iz/Ag+in CH3CN at 0 "Clbor with KWIZin EtaO at -78 "C (Table 1). The selectivity in all cases using PhSeCl or IZwas on the order of 2:l or less, while KWIZ gave ratios that were significantly improved, along with good isolated yields.' Other, nonethereal solvents (eg., CHZC12, PhCH3, DMF) at low temperatures (between 0 and -78 "C) gave inferior results. In general, cyclizations of enol ethers proceeded in a short period of time ( < l o min) even when an electron-withdrawing group was present in the enol ether (entry 3h8 Diastereoselectivity was somewhat higher with (E)-rather than (2)-enol ethers (compare entries 1and 4)) and protecting groups at the side-chain position were of no consequence (entries 4, R = Bn us entry 6, R = thexyldimethylsilyl). Placement of a bulky substituent such as the MezSi(0t-Bu) group in the allylic position (13)bearing an anti disposition relative to the adjacent hydroxyl group raised the diastereoselectivity of 14d14b to '955 (Scheme 2),9 while placement of this residue in the syn arrangement (16)led to no net enhancement (85:15, 83% yield).1° Reductive removal of the iodide from the products of cyclization readily occurred via BusSnH treatment. Silicon substituents such as that in 14d14b could be further reduced to dideoxyriboside 15dl5b using fluoride ion in hot DMF (Scheme 21." Given the ease with which acetylenic ethers (e.g., 17) can be c o n ~ t r u c t e d ,application ~,~ of the methodology to disaccharide formation using glucose derivative 19 was next considered. Interestingly, this more complex educt cyclized under standard conditions (i.e.,KH, 12, EbO, -78 "C) to afford a r95:5 mix of product 2,5-trans 21a:2,5cis 21b (R = H) isomers (Scheme 3).12 The effect of an additional substituent at carbon bearing the free hy(3)For the synthesis of 3a see: (a)Anisuzzaman, A. K. M.; Owen, L. N. J. Chem. SOC.C 1967,1021. (b) Takano, S.;Goto, E.; Hirama, M.; Ogasawara, K. Heterocycles 1981, 16,381. Compound 3b was synthesized by treatment of glycidol (Aldrich Corp.) with thexyldimethylsilyl chloride/imidazole in CHzClz (87% yield; see Experimental Section). (4) Skrydstrup, T.; Benechie, M.; Khoung-Hung, F. Tetrahedron Lett. 1990,31,7145. ( 5 ) Fried, J.; Sih, J. C.; Dalven, P.; Lin, C. J.Am. Chem. SOC.1972, 94,4343. (6)Moyano, A.; Charbonnier, F.; Greene, A. E. J . Og.Chem. 1987, 52,2919. (7)Attempts using other bases (e.g., NaH, KO-t-Bu) failed to increase the selectivity of the reaction in EtzO. Only NaH in THF was equally effective, judging from the one case examined ( i e . , Table 1, entry 4; ratio: 6:l).Selectivity also was not improved using nonbasic conditions and/or different electrophiles (e.g., 12 or PhSeCVZnBrz, (collidine)zI+C104-,NIS). (8)The reaction of a homoallylic alcohol as described in ref l b for 8 h under our standard conditions (KH, EtzO, 12, -78 "C) led to 20% recovered educt (ratio of stereoisomers: 1O:l). (9)Only one isomer was detected and subsequently isolated. (10)Reactions of anti-13 and syn-16 with 12 or PhSeCl in CH&N produced only a complex mixture of products. Compounds 13 and 16 were synthesized by treatment of (E)-or (Z)-l-(benzyloxy)-3-(tertbutoxydimethylsilyl)-2,3-epoxypropane(27 and 31,respectively; see supplementary material) with an alanate reagent followed by reduction of the acetylenic ether with Lindlar catalyst as described in the Experimental Section. (11)Hale, M. R.; Hoveyda, A. H. J . Org. Chem. 1992,57,1643and references therein. (12)Compounds 17 and 18 were synthesized by treatment of (I?)(+)-glycidolor (I?)-2-methylglycidol(Aldrich) with benzyl bromide/NaH in THF (60% yield) followed by the reaction with an alanate reagent in toluene (65-70% yield; cf. Experimental Section for this epoxide transformation).
0022-326319411959-8307$04.5010 0 1994 American Chemical Society
8308 J. Org. Chem., Vol. 59, NO.26, 1994 droxyl (i.e.,educt 20) was also studied with this system. The high diastereoselectivity realized with 19 was essentially lost in the conversion of 20 to 21d21b (R= Me), as expected due to the similarity in steric demand of each of the two substituents. Stereochemical assignments for these cyclizations were made on the basis of (1) data acquired via chemical correlation, ( 2 )relative chemical shift data, and (3) NOE experiments. Our previous reliance solely on this latter technique for assigning stereochemistry in tetrahydrofurans demonstrated just how sensitive these measurements can be to the conditions of an NOE experiment.lb Indeed, we were misled by the results from these earlier studies resulting in several incorrect assignments and conclusions regarding iodocyclizations of homoallylic alcohols, which have since been corrected.laJ3 Stereochemical assignments herein could be made by taking advantage of the known additions of nucleophiles to furanose glycals (e.g.,22) under the influence of I+, which occur selectively in a trans fashion with the electrophile approaching predominantly from the a-face to give iodohydrin derivatives 7d7b.I4 Thus, in the presence of cyclohexanol as nucleophile, products of anti addition were obtained in a 1:14ratio (Scheme 4). Recalling that cyclization of enol ether Sa led to the same two products 7 d 7b, it was clear by NMR that major product 7b from 22 was identical to the minor product obtained from 5a.15 Furthermore, removal of iodide with BusSnH from each of the products 10a and 7a, as with silyl-substituted 14d 14b, led to dideoxyriboses 15a and 15b, respectively. Hence, (E)-enol ethers afford 2,5-trans dideoxyribosides, while (2)-isomers lead to the corresponding 2,5& analogs. In sum, it has been demonstrated for the first time that &hydroxy (E)- and (2)-enol ethers can be cyclized to afford mainly 2,5-trans or 2,5& dideoxyriboses, respectively, via treatment with KWI2.l8 The more commonly used conditionsla-' of PhSeCl and Id&+ are not effective for closures in this system. Incorporation of a sugar in (13)A re-evaluation of the iodocyclizations previously reported by uslb and later confirmedla revealed poor selectivities (60:40 to 80:20) and exclusively trans addition of I+ and the hydroxyl group to the olefin. A paper claiming high selectivitiesusing our original conditions (Le,,12 in CH3CN),however, has just appeared; cfi Barks, J. M.; Knight, D. W.; Seaman, C. J.; Weingarten, G. G. Tetrahedron Lett. 1994,35, 7259. (14) (a) Kim, C. U.;Misco, P. F. Tetrahedron Lett. 1992, 33, 5733. (b) Wang, J.; Wurster, J. A,; Wilson, L. J.; Liotta, D. Zbid. 1993, 34, 4881. (15)According to the method of Williams,16stereochemical assignments could be made based on the Ad values for the nonequivalent protons at C-4 in product iodotetrahydrofurans. For those products bearing a cis relationship between iodine at C-3 and the C-5 residue (in 7a-l2a), Ad was found in all cases to be 20.40 ppm, while for those of trans configuration (for 7b-l2b), Ad 5 0.20 ppm, fully supporting the assignments from chemical correlations (vide supra).14 The C-2, C-3 relationships follow as well from the deshielding effect of the C-3 halogen cis to the proton at the anomeric center (6 2 5.3 ppm) relative to the alternative trans orientation (6 5 5.0 ppm).17 Lastly, careful NOE experiments on 7a and 10a (see supplementary material) were in line as well with the above analyses. (16) Williams, D. R.; Harigaya, Y.; Moore, J. L.; D'sa, A. J . Am. Chem. SOC.1984, 106, 2641; see also ref la. (17) Lambert, J. B. Organic Structural Analysis; MacMillan: New York, 1976; pp 33-34. (18) For related work on the syntheses of isotopically labeled ribose derivatives and their incorporation into ribonucleosides see: (a)Jung, M. E.; Gardiner, J. M. Tetrahedron Lett. 1994,35, 6755. (b) Goering, B. K.; Lee, K.; An, B.; Cha, J. K. J. Org. Chem. 1993, 58, 1100. (c) Hodge, R. P.; Brush, C. K.; Harris, C. M.; Harris, T. M. ibid. 1991,56, 1553 and references therein. For related work on the synthesis of substituted y-lactones which proceeds via cyclizatiodoxidation of y-hydroxy enol carbamates, see: (a)Rehders, F.; Hoppe, D. Synthesis, 1992, 859. (b) Hoppe, D.; Bronneke, A. Tetrahedron Lett. 1983, 24, 1687.
Notes
Scheme 1 R O W o
[Me#-
CORq-Li+
PhCH3, O°C to rt 3s,R;.Bn (5565%) 3b,R = (thexyl)SiMe2
OH _..
4
1
-O R OH
P
5 (55-60%)
OH 6 (8045%)
the enol ether can be employed as an inroad to disaccharide formation. Further applications of these electrophilically-driven cyclizations to nitrogen-containing substrates is in progress and will be reported in due course.
Experimental Section General Procedure. All reactions were performed in ovendried glassware equipped with a magnetic stirring bar under a positive pressure of dry argon using standard syringe techniques. All reagents were purchased from the Aldrich Chemical Co. and were purified and dried prior to use. Tetrahydrofuran (THF) and diethyl ether were distilled from sodiumhenzophenone immediately prior to use. Toluene and DMF were distilled from CaHz. Mass spectra were run on either a VG-Autospec at the UCLA campus or an analytical VG 70-250 HF instrument. Proton magnetic resonance spectra (500 MHz) were recorded with a General Electric GN-500 spectrometer as solutions in deuteriochloroform and recorded in ppm from tetramethylsilane with the solvent resonance as an internal standard (7.24ppm). Carbon-13 magnetic resonance spectra (125MHz) were recorded with a General Electric GN-500 spectrometer with proton decoupling as solutions in deuteriochloroform and recorded in ppm from tetramethylsilane with the solvent resonance as a n internal standard (77.0ppm). Column chromatography was performed with silica gel 60 (32-63 mesh, ICN Biomedical), and TLC was run on silica gel 60 F-254plates (Merck). Epoxide 3b. To a round-bottom flask containing glycidol(2.5 mL, 37 mmol), imidazole (2.5g, 37 mmol), and CHzClz (300mL) was added (thexy1)dimethylsilyl chloride (5.0mL, 25 mmol) dropwise. After 2 h the reaction was filtered, washed with brine (2x1,and then dried over anhydrous NazSO4. Filtration and solvent removal in U ~ C U Owas followed by purification by column chromatography (mixture of hexanes/EtzO) to obtain 4.7g (87%) of 3b: 'H N M R (CDCl3) 6 3.79 (dd, J = 11.9,3.1 Hz, 1 H), 3.61 (dd, J = 11.9,4.7 Hz,1 H),3.04(m, 1 H),2.73 (dd, J = 5.1,4.1
Hz,1H),2.60(dd,J=5.1,2.7Hz,1H),1.60(m,1H),0.86/0.85 ( 8 , 6 H), 0.09/0.08 ( 8 , 6 H); 13C N M R (CDC13) 6 63.4,52.4,44.5, 34.1,25.5, 20.2, 18.5, -3.5; HRMS (EI) calcd for C5H1102Si [M - CeH131+ 131.0525,found 131.0543. General Procedure for the Opening of an Epoxide with an Alanate Reagent. To a round-bottom flask containing the acetylenic ether (12.3mmol) and toluene (80mL) at 0 "C was added n-BuLi (6.5mL, 13 mmoL, 2.0M) dropwise. Mer 30 min, Me& (6.2mL, 12.3 mmol, 2.0 M in toluene) was added to the solution. Following a 4 h period, the epoxide (6.2mmol), diluted in 4 mL of toluene, was introduced and the reaction was stirred overnight at rt. The reaction was quenched dropwise with an aqueous saturated solution of NaHC03 and then diluted with EtzO. The aqueous phase was extracted with Et20 (2x1,and the combined organic layers were washed with brine and then dried over anhydrous Na2S04. Filtration and solvent removal in vacuo was followed by purification by column chromatography (mixture of hexanes/EtzO with 2% Et3N as eluent) to obtain the desired product. Acetylenic ether 4a; R = benzyl, R = cyclohexyl: 'H N M R 6 7.30-7.24 (m, 5 H), 4.57(s,2 H), 3.95 (m, 1 H),3.87 (m, 1 H), 3.60 (dd, J = 9.5,4.1 Hz, 1 H), 3.48 (dd, J = 9.5,6.6 Hz, +
J. Org. Chem., Vol. 59,No. 26, 1994
Notes
8309
Table 1. Comparison of g W I 2 with Iodo- and Selenocyclizationsof S-Hydroxy (E)- and (2)-EnolEthers 5 and 6
Ratka (yield%)b Entry
EductC
R'
KHIIpd
I2/Ag+e
P-le
1
sa
cycbhexyl
91:9 (83)f
66:34(82)
60:40(-)9
2
sb
-(CH2)3m
89:ll (75)
88:s(-)g
products 7 m 8dBb
I
3
sc
&naphthyl
88:12 (80)
4
ea
cycbhexyl
85:15 (85)
5
6b
-(CH2)3m
6416 (79)
(a :b) 6436 (-)Q
lodlob
88:33(-)Q
llalllb 1
6
60:40(-)g
85% (82)
cycbhexyl
6Ch
@am
60:40(-)Q
(a :b)
12d12b
Refers to series of products (a:b);determined by lH NMR of the crude mixture. Isolated yield of both isomers &r chromatography. R = benzyl, unless otherwise indicated. Reaction was carried out in EhO at -78 "C. e Reaction was carried out according to ref lb. f Use of THF instead of Et20 resulted in a decrease in diastereoselectivity (85:15). 8 Yield not determined. h R = thexyldimethylsilyl.
Scheme 2
Scheme 4
13
14a
(>95:5)
144
1. Bu3SnH (79%) 2. CsFKBAFIDMF (73%) 1 s (r95:5) lsb (R' = cycbhexyi)
OH OR' sa (R' = cycbhexyl)
Me2(t-Bu0)Si OH 10 (R' = cycbhexyl)
Scheme 3
K0
0
19,R-H
17, R = H 18, R = Me
KH, I 2
+ 2,5-cisisomer 21b
(75%)
0x0 218
from 19, R = H from 20, R = Me
58:42
[75:25 using IdAg' in CHsCN]
1H), 2.41 (m, 2 H), 2.0-1.0 (m, 10 H); 13C NMR 6 128.4, 127.7, 89.9, 85.7, 73.4, 73.1, 69.5, 30.9, 25.1, 23.2, 22.6; HRMS (CI! NHs) calcd for C18H2503 [M HI+ 289.1804, found 289.1803.
+
14
M20, -78OC
10
1
Acetylenic ether 4b; R = benzyl, R = (CHahPh: 'H NMR 6 7.5-7.0 (m, 10 HI, 4.55 (9, 2 HI, 3.97 (t,J = 6.3 Hz, 2 H), 3.88 (m, 1 H), 3.59 (dd, J = 9.5, 4.0 Hz, 1 H), 3.48 (dd, J = 9.5, 6.7 Hz, 1H), 2.70 (t,J = 7.6 Hz, 2 H), 2.40 (m, 3 HI, 2.01 (m, 2 HI; 13CNMR6 137.9,128.4, 127.6,126.1,91.2,77.3,73.4,73.0,69.4, 32.8, 31.4, 30.3, 22.4; HRMS ~CI/NH3)calcd for C21Hz503 [M + H]+ 325.1804, found 325.1806. Acetylenic ether 4c; R = benzyl, R = /%naphthyl:lH NMR 6 7.80 (m, 3 H), 7.69 (d, J = 2.4 Hz, 1 HI, 7.5-7.4 (m, 2 H), 7.36-7.27 (m, 6 H), 4.61 ( 8 , 2 HI, 4.04 (m, 1HI, 3.69 (dd, J = 9.5, 3.9 Hz, 1 H), 3.59 (dd, J = 9.5, 6.6 Hz, 1H), 2.65-2.47 (m, 3 H), 1.03 (t, J = 7.2 Hz, 1 H); 13C NMR 6 153.9, 137.8, 133.8,130.6,129.8,128.4,127.8,127.7,127.2,126.9,125.1,116.0, 110.1, 84.9, 73.5, 73.1, 69.4, 40.9, 22.5; HRMS (CIMH3) calcd for C22H21O3 [M HI+ 333.1491, found 333.1489. Acetylenic ether 4d; R = thexyldimethylsilyl,R' = cy. clohexyl: lH NMR 6 3.93 (m, 1 H), 3.66 (m, 2 H), 3.56 (m, 1 H), 2.33 (m, 3 HI, 2.0-1.0 (m, 9 HI, 0.85 (m, 12 HI, 0.10 (m, 6 H); 13C NMR 6 89.9,85.6,70.8,65.4,34.2,33.7,30.9,25.1,23.2, 22.1,20.3,20.1, 18.5, -3.5; HRMS (EI) calcd for C13H2703Si [M - CsH# 259.1722, found 259.1742. Acetylenic ether 17; R = H, R' = diacetone-D-glucose: 1H NMR 6 7.3-7.2 (m, 5 H), 5.89 (d, J = 3.7 Hz, 1H), 4.85 (d, J = 3.8Hz, 1HI, 4.57 ( s , 2 HI, 4.47 (d,J= 2.6Hz, 1HI, 4.31 (m, 1 H), 4.12-4.07 (m, 2 H), 4.02 (dd, J = 8.8, 4.6 Hz, 1 H),3-90 (m, 1H), 3.57 (dd, J = 9.5, 4.2 Hz, 1 H), 3.48 (dd, J = 9.5, 6.5 Hz, 1 H), 2.40 (d, J = 6.2 Hz, 2 HI, 1.50 ( 8 , 3 HI, 1.44 (8, 3 H), 1.36 ( ~ ,H), 3 1.33 ( s , 3 HI; HRMS (CVNH3) calcd for C24H3608N [M N&l+ 466.2440, found 466.2441. Acetylenic ether l&R = Me, R' = diacetone-D-glucose: 1H NMR 6 7.3-7.2 (m, 5 H), 5.89 (d, J = 3.7 Hz,1HI, 4.84 (d, J = 3.7 Hz, 1H), 4.58 (s,2 HI, 4.45 ( d , J = 2.6 Hz, 1H), 4.31 (m, 1H), 4.12-4.07 (m, 2 H), 4.03 (dd, J = 8.8,4.5 Hz, 1H), 3.42 (d, J = 8.9 Hz, 1H), 3.36 (d, J = 8.9 Hz, 1H), 2.43 ( d , J = 16.2 Hz, 1 H), 2.37 (d, J = 16.2 Hz, 1H), 1.50 (a, 3 H), 1.43 (s, 3 H), 1.35
+
BnO
820,-78OC
-
Bno7q(
1
KH, 12
+
8310 J. Org. Chem., Vol. 59,No. 26, 1994
Notes
3 H), 1.32 (s, 3 H), 1.25 (s, 3 HI; 13C NMR 6 138.1, 128.4, 127.6,127.5,112.3,109.5,104.8,89.3,88.3,81.9,79.9, 75.9, 73.4,
(8,
71.7, 71.6, 67.0, 35.2, 28.2, 26.9, 26.6, 26.2, 25.1, 23.8; HRMS (CVNH3)calcd for CZSH3608 [M HI+ 463.2287, found 463.2289.
+
General Procedure for the Reduction of a S-Hydroxy Acetylenic Ether to an (E)-b-HydroxyEnol Ether. To a round-bottom flask containing a &hydroxy acetylenic ether (1.2 mmol) and 12 mL of THF a t 0 "C was added LiAlH4 (0.84 mL, 0.84 mmol, 1.0 M in THF) dropwise. The reaction was allowed to reach rt and followed by TLC. When complete, it was quenched dropwise with a saturated aqueous solution of NaHCO3, and the aqueous phase was extracted with EtzO (2x). The organic layers were combined and washed with brine and then dried over anhydrous Na2S04. After filtration and solvent removal in vacuo the residue was purified by chromatography (mixture of hexanes/EtzO with 2% Et3N as eluent) to afford the expected product. (E)-&Hydroxyenol ether Sa; R = benzyl, R' = cyclohexyl: lH NMR 6 7.30-7.24 (m, 5 H), 6.16 (d, J = 12.4 Hz, 1 H), 4.83 (m, 1H), 4.57 (m, 2 HI, 3.77 (m, 1HI, 3.64 (m, 1HI, 3.51 (dd, J = 9.5, 3.5 Hz, 1H), 3.38 (dd, J = 9.5, 7.2 Hz, 1H), 2.13 (m, 2 H), 1.9-1.2 (m, 10 H); 13CNMR 6 147.1,128.4,127.7, 100.5, 78.2, 73.6, 73.3, 70.4, 32.0, 31.9, 25.5, 23.7; HRMS (EI) calcd for C12H1502 [M - OCeH11]+ 191.1068, found 191.1072. (E).S.Hydroxy enol ether 6b; R = benzyl, R = (CH2)SPh: 1H NMR 6 7.5-7.0 (m, 10 HI, 6.29 (d, J = 12.6 Hz, 1HI, 4.71 (m, 1H), 4.55 (s,2 H), 3.76 (m, 1HI, 3.65 (t,J = 6.3 Hz, 2 H), 3.51 (dd, J = 9.5, 3.5 Hz, 1H,), 3.38 (dd, J = 9.5, 7.1 Hz, 1 H), 2.70 (t, J = 7.7 Hz, 2 H), 2.13 (m, 2 H), 1.96 (m, 2 H); 13C NMR 6 148.3, 141.5, 137.9, 128.4, 127.7, 125.8,98.7, 73.7, 73.3, 70.5,68.2, 32.1,31.9,30.8; HRMS (CI/NH3) calcd for C21H3003N [M NH4]+ 344.2226, found 344.2235. (E)-&Hydroxyenol ether Sc; R = benzyl, R' = B-naphthyl: 1H NMR 6 8.0-7.0 (m, 12 H), 6.63 (d, J = 12.1 Hz, 1H), 5.43 (dt, J = 12.1, 7.9 Hz, 1H), 4.58 (s, 2 H), 3.90 (m, 1HI, 3.59 (dd, J = 9.5, 3.4 Hz, 1H), 3.45 (dd, J = 9.5, 7.0 Hz, 1H), 2.30 (t,J = 7.2 Hz, 2 H); 13CNMR 6 154.9, 143.5,137.9, 134.2, 129.8, 129.7, 128.4, 127.7, 126.9, 126.5,124.3,118.5,110.6,108.7,73.7, 73.4, 70.1, 31.4; HRMS (CI/NH3) calcd for C22HZZ03 [M + HI+ 334.1564, found 334.1569. (E)-&Hydroxyenol ether 19 lH NMR 6 7.3-7.2 (m, 5 HI, 6.20 (d, J = 12.5 Hz, 1H), 5.84 (d, J = 3.7 Hz, 1H), 4.91 (dt, J = 12.5, 7.7 Hz, 1HI, 4.58 (m, 3 HI, 4.45 (m, 2 HI, 4.13 (m, 1HI, 4.05 (dd, J = 13.6, 6.2 Hz, 1H), 4.00 (dd, J = 8.6, 5.2 Hz, 1H), 3.78 (m, 1H), 3.47 (dd, J = 9.5, 3.7 Hz, 1H), 3.36 (dd, J = 9.4, 7.0 Hz, 1H), 2.20 (m, 2 H), 1.49 (s, 3 HI, 1.41 ( 8 , 3 H), 1.32 (s, 3 H), 1.29 (s,3 H); 13CNMR 6 146.2, 137.8, 128.2, 127.5, 111.7,
+
(2)-&Hydroxy enol ether 6b; R = benzyl, R = (CH2)sPh: lH NMR 6 7.4-7.2 (m, 10 H), 6.04 (d, J = 6.0 Hz,1 H), 4.56 (s, 2 H), 4.42 (m, 1H), 3.87 (m, 1H), 3.72 (t, J = 6.4 Hz, 2 H), 3.53 (dd, J = 9.5, 3.6 Hz, 1H), 3.40 (dd, J = 9.5, 7.5 Hz, 1H), 2.69 (t, J = 7.6 Hz, 2 H), 2.31 (t,J = 7.0 Hz, 2 H), 1.92 (m, 2 H); HRMS (CI/NH3) calcd for C21H3003N [M + NH41+ 344.2226, found 344.2220. (Z).&Hydroxyenol ether 6c;R= thexyldimethylsilyl,R = cyclohexyk 'H NMR 6 6.08 (d, J = 6.3 Hz, 1H), 4.39 (m, 1 H), 3.7-3.5 (m, 3 H), 3.42 (dd, J = 9.9, 6.8 Hz, 1H), 2.24 (m, 2 H), 1.8-1.2 (m, 11H), 0.85 (m, 12 H), 0.10 (m, 6 H); 13C N M R 6 145.3, 101.6, 79.2, 71.9,66.5, 34.2,32.2,27.9,25.5,23.5,20.3, 18.5, -3.5; HRMS (CVNH3) calcd for C19H4~03SiN[M NH4]+ 360.2934, found 360.2923. (Z)-&Hydroxyenol ether 13: lH NMR 6 7.4-7.25 (m, 5 H), 6.09 (d, J = 6.3 Hz, 1H), 4.60 (d, J = 12.1 Hz, 1H), 4.51 (d, J = 12.1 Hz, 1H), 4.48 (dd, J = 10.9, 6.3 Hz, 1H), 4.18 (m, 1
+
H),3.6-3.5(m,2H),3.44(dd,J=9.6,4.4Hz,lH),2.14(dd,J = 10.9, 2.7 Hz, 1H), 1.9-1.3 (m, 10 H), 1.25 ( 8 , 9 H), 0.23/0.19 (s,6 H); l3C NMR 6 143.5,138.7,128.2,127.7,127.3,100.9,79.0, 74.6, 73.3, 70.3, 32.4, 32.3, 31.8, 30.3, 25.5, 23.7, 0.81, 0.28;
HRMS (FAB)calcd for C2pH4004Si [MI+420.2638, found 420.2695. (Z)-l-Hydroxyenol ether 16: 'H NMR 6 7.4-7.3 (m, 5 HI, 6.03 (d, J = 6.3 Hz, 1H), 4.65 (d, J = 12.2 Hz, 1H), 4.59 (d, J = 12.2 Hz, 1H), 4.10-4.02 (m, 2 H), 3.65 (dd, J = 10.0,2.1 Hz, 1H), 3.59 (m, 1H), 3.43 (dd, J = 10.0, 7.3 Hz, 1H), 2.42 (dd, J = 10.5, 10.4 Hz, 1H), 1.9-1.4 (m, 10 H), 1.32 (e, 9 H), 0.25/0.23 (s, 6 H); 13C NMR 6 143.6, 138.8, 128.2,127.7, 127.2, 101.9, 79.1, 74.9,73.3,72.2,32.4,32.3,31.8,30.6,25.5,23.6,23.6,0.68, -1.0; HRMS (FAB)calcd for C~oH3103Si[M 1- t-BuOHl+ 347.2026, found 347.2042.
+
General Procedure for the Cyclization of a &Hydroxy Enol Ether. To. a round bottom flask cooled to -78 "C and containing KH (48 mg, 0.42 mmol, 35% in oil) and 2.4 mL of Et20 was added dropwise the &hydroxy enol ether (0.20 mmol) diluted in 2.4 mL of EtzO. Then, a solution of 1 2 (262 mg, 1.03 mmol) in 2.4 mL of Et20 was added and the reaction was followed by TLC. After completion (< 10 min) the cold bath was removed and the reaction was diluted with EtzOEtaN and quenched with an aqueous saturated solution of NazSz03 (for better results in the case of 9d9b and 21a/21b, a saturated solution of NazSz03 was added dropwise to remove excess iodine, Le., until the red color disappeared). The aqueous phase was extracted with Et20 (2x1 and the combined organic layers were washed with brine and dried over anhydrous NazSO4. The solvent was then evaporated in uocuo. The resulting crude material was analyzed by lH NMR and then purified by column chromatography to obtain the expected products (mixture of 108.9, 104.8, 101.9,82.1, 81.1, 80.3, 73.4, 73.1, 71.9, 69.9, 66.8, hexanes/EtzO with 2% Et3N as eluent). 31.6, 26.6,26.5,26.0,25.1; HRMS (CI/NH3)calcd for C24H38Oa Iodotetrahydrofuran?a; R = benzyl, R' = cyclohexyl: [M N&]+ 468.2597, found 468.2592. Rf 0.20, 10% ethyl etherhexanes; lH NMR 6 7.3-7.2 (m, 5 H), (E)-&Hydroxyenol ether 20: lH NMR 6 7.3-7.2 (m, 5 H), 5.44 (s, 1H), 4.64 (d, J = 12.2 Hz, 1H), 4.58 (d, J = 12.2 Hz, 1 6.17 (d, J = 12.5 Hz, 1H), 5.87 (d, J = 3.7 Hz, 1H), 4.94 (m, 1 H), 4.41 (m, 1H), 4.08 (m, 1H), 3.72 (dd, J = 10.1,6.3 Hz, 1H), H), 4.55 (m, 3 H), 4.26 (m, 2 H), 4.14 (dd, J = 8.0, 2.8 Hz, 1H), 3.60 (m, 2 H), 2.83 (m, 1 H), 2.16 (m, 1 HI, 1.9-1.5 (m, 10 H); 4.07 (dd, J = 8.7, 6.1 Hz, 1H), 4.02 (dd, J = 8.7, 5.1 Hz, 1HI, 13C NMR 6 138.4, 128.4, 127.8, 127.7, 109.4, 75.3, 73.4, 72.1, 3.34 (dd, J = 8.9, 2.8 Hz, 1H), 3.28 (d, J = 8.9 Hz, 1HI, 2.18 38.9, 33.6,31.8,25.6, 24.2,24.0,22.8; HRMS (CI/NH3)calcd for (dd, J = 13.9, 7.7 Hz, 1H), 2.11 (dd, J = 13.9,8.2 Hz, 1H), 1.51 C18H29031N[M NH4]+ 434.1192, found 434.1188. (s, 3 H), 1.42 (s, 3 HI, 1.33 (s, 3 HI, 1.31 ( 8 , 3 HI, 1.15 ( 8 , 3 HI; Iodotetrahydrofuran7b; R = benzyl, R = cyclohexyl: 13C NMR 6 146.9,138.1,128.4,127.7,127.6,111.9,109.2,105.1, Rf 0.26, 10% ethyl etherhexane; 'H NMR 6 7.3-7.2 (m, 5 HI, 101.7, 82.5, 81.4, 80.6, 73.5, 72.1, 71.9, 67.1, 37.3, 26.9, 26.8, 5.47 (s, 1H), 4.59 (m, 3 H), 4.16 (d, J = 5.5 Hz, 1H), 3.63-3.50 26.2, 25.2, 23.8; HRMS (CI/NH3) calcd for C25H3708 [M HI+ (m, 3 H), 2.34 (m, 1H), 2.26 (m, 1H), 1.9-1.5 (m, 10 H); 13C 465.2443, found 465.2463. NMR 6 138.1, 128.3, 127.7, 127.6, 108.7, 78.4, 75.1, 73.3, 73.2, General Procedure for the Reduction of a &Hydroxy 38,3,33.5,31.8,26.3,25.6,24.2,23.9; MS (CVNH3)for C18H2903Enol Ether. A mixture Acetylenic Ether to a (Z)-S-Hydroxy IN [M NHil 434.1. of freshly distilled quinoline (0.2 mL), 100 mg of Lindlar catalyst, Iodotetrahydrofuran8a; R = benzyl, R' = (CHdsPh Rf and the &hydroxy acetylenic ether (1.5 mmol) in 30 mL of dry 0.15, 10% ethyl etherhexanes; 'H NMR 6 7.5-7.0 (m, 10 H), hexane was exposed to Hz gas using a filled rubber ballon. After 5.36 (s, 1H), 4.62 (d, J = 12.3 Hz, 1H), 4.56 (d, J = 12.0 Hz, 1 ca. 30 min (TLC), the reaction mixture was filtered and purified H), 4.38 (m, 1 H), 4.09 (m, 1 H), 3.70 (m, 1 HI, 3.59 (dd, J = by column chromatography (mixture of hexanes/Et2O with 2% 10.2,4.6 Hz, 1H), 3.42 (dt, J = 9.7,6.5 Hz, 1H), 2.80 (m, 1HI, Et3N as eluent). 2.65 (m, 2 H), 2.14 (m, 1H), 1.86 (m, 2 HI; 13C NMR 6 141.7, 138.0, 128.4, 128.3, 127.8, 127.7, 125.8, 111.5, 77.5, 73.4, 71.9, (Z)-6-Hydroxyenol ether Ba; R = benzyl, R' = cyclo67.1, 39.0, 32.3, 31.2, 21.7; HRMS (EI) calcd for CzlH25031 [M+l hexyl: 'H NMR 6 7.30-7.24 (m, 5 H), 6.08 (d, J = 5.9 Hz, 1H), 452.0848, found 452.0860. 4.54 (s, 2 H), 4.38 (m, 1H), 3.84 (m, 1H), 3.58 (m, 1H), 3.49 Iodotetrahydrofuran8b; R = benzyl, R = (CHdsPh Rf (dd, J = 9.6, 3.8 Hz, 1H), 3.38 (dd, J = 9.6, 7.4 Hz, 1H), 2.28 0.21, 10% ethyl etherhexanes; lH NMR 6 7.5-7.0 (m, 10 H), (m, 2 H), 1.8-1.2 (m, 10 H); I3C NMR 6 145.6, 138.2, 128.4, 5.30(s,lH),4.59-4.54(m,3H),4.17(d,J=5.6Hz,lH),3.66 127.6, 127.5, 101.2, 79.3, 74.2, 73.3, 70.6, 32.2, 28.4,25.5, 23.5; (dt, J = 9.6, 6.4 Hz, 1H), 3.56 (dd, J = 10.0, 6.3 Hz, 1H), 3.51 HRMS (CI/NH3) calcd for C18H2703 [M HI+ 291.1960, found (dd, J = 10.0, 4.7 Hz, 1H), 3.36 (dt, J = 9.6, 6.5 Hz, 1H), 2.58 291.1964.
+
+
+
+
+
J. Org. Chem., Vol. 59,No. 26, 1994 8311
Notes (m, 2 H), 2.30(ddd, J = 14.3,8.9,5.8Hz, 1 H),2.24(ddd, J = 14.3,6.2,0.9Hz, 1 H), 1.80(m, 2 H); 13C NMR 6 141.7,128.4,
Iodotetrahydrofuran14a: IH NMR 6 7.4-7.25(m, 5 H), 4.98(d, J = 3.9Hz,1 H),4.59(d, J = 12.2Hz, 1 H), 4.55(d, J 127.7,125.8,110.7,78.7,73.3,73.0,66.7,38.2,32.3,31.2,25.3; = 12.2Hz,1 H), 4.27(m, 1 H), 3.87(dd, J = 12.4,3.9Hz,1 HI, MS (CVNH3) for Cz1Hzs03IN [M + m4If 470.1. 3.64(m, 1 H), 3.54-3.46(m, 2 H), 1.8-1.3(m, 11 H), 1.21(9, 9 H), 0.2W.026( 8 , 6 H); 13C NMR 6 138.4,128.3,127.8,127.5, IodotetrahydrofuranSa; R = benzyl, R' = /3-naphthyl: 101.4,81.6,75.4,74.9,73.3,35.8,33.3,31.9,31.0,25.8,23.8, Rf 0.15,10% ethyl etherhexanes; IH NMR 6 7.75(m,3 H), 23.6,2.2,0.41;HRFAB calcd for C24H3804ISi [M + 1 - Hzl) 7.45-7.15(m, 9 HI, 6.16( 8 , 1 HI, 4.62( s , 2 HI, 4.59 (m, 1 HI, 545.1631,found: 545.1584. 4.41(m, 1 H), 3.79 (dd, J = 10.3,5.7Hz, 1 HI, 3.71(dd, J = Iodotetrahydrofuran 21a (R = H): Rf0.42,50% ethyl 10.3,4.9Hz, 1 H), 2.98(m, 1 H), 2.35(ddd, J = 14.3,6.4,4.7 etherhexanes; IH NMR 6 7.3-7.2(m, 5 HI, 5.83(d, J = 5.6Hz, Hz, 1 H);13C NMR 6 153.9,134.3,129.6,129.5,128.4,127.8, 1 H), 5.63(8, 1 H),4.64(d, J = 12.2Hz, 1 H), 4.59(d, J = 12.2 127.7,127.6,127.2,126.4,124.2,119.0,110.8,109.9,78.8,73.5, Hz, 1 H), 4.56(d, J = 3.5Hz, 1 H),4.41(m, 1 H), 4.23(d, J = [M + NH41+ 71.5,38.7,21.1;HRMS (CI/NH3) for CZZHZSO~IN 3.0Hz, 1 H),4.19(m, 1 H), 4.12(m, 2 H), 4.06(dd, J = 8.4,2.8 calcd 478.0879,found 478.0880. Hz,lH),3.94(dd,J=8.4,5.8Hz,lH),3.74(dd,J=10.2,6.0 IodotetrahydrofuranSb; R = benzyl, R' = /%naphthyl: Hz, 1 H), 3.64(dd, J = 10.2,4.8 Hz, 1 H), 2.80(m, 1 H), 2.18(m, Rf0.21,10%ethyl etherhexanes; 'H NMR 6 7.75(m, 3H), 7.451 H), 1.49( 8 , 3 H),1.42(9, 3 H), 1.37( s , 3 HI, 1.30( s , 3 HI; 13C 7.15(mult, 9 H), 6.14( 8 , 1 H), 4.78(m, 1 H), 4.45-4.51(m, 3 NMR6 137.9,128.4,127.7,127.6,111.9,109.2,105.3,84.0,81.3, H), 3.63(dd, J = 10.4,5.9Hz, 1 H), 3.59(dd, J = 10.4,4.7Hz, 80.0,78.0,73.5, 72.2,71.7,67.7,38.9,26.9,26.7,26.2,25.5,20.4; 1 H), 2.58(ddd, J = 14.6,9.0,5.8Hz, 1 H), 2.39(dd, J = 14.6, 6.0Hz, 1 H);13C NMR 6 153.8,138.0,134.3,129.5,128.2,127.5, HRMS (CI/NH3) calcd for C24H3708IN [M + NH41+ 594.1563, found 594.1541. 127.1,126.4,124.2,118.9,110.4,108.9,80.1,73.4,72.4,37.8, Iodotetrahydrofuran 21b (R = H): Rf0.48,50% ethyl 24.8;MS (CVNH3) calcd for Cz2Hz1031 [MI+ 460.1,found 460.1. etherhexanes; 'H NMR 6 7.3-7.2(m, 5 H), 5.84(d, J = 3.7Hz, Iodotetrahydrofuranloa; R = benzyl, R = cyclohexyl: 1 H), 5.51(s, 1 H),4.7-4.5(m, 4 H), 4.37(d, J = 3.1Hz, 1 H), Rf0.48,40% ethyl etherhexanes; IH NMR 6 7.3-7.2(m, 5 H), 4.21-4.10(m, 3 H), 4.03(dd, J = 8.5,6.4Hz, 1 H), 3.95(dd, J 5.02(d, J = 4.1Hz, 1 H), 4.56(m, 2 H), 4.24(m, 1 H), 3.96(ddd, = 8.5,5.8Hz, 1 H),3.77(dd, J = 10.2,6.6Hz, 1 H), 3.63(dd, J J = 12.1,7.1,4.1Hz,1 H), 3.61(m, 1 H), 3.58(dd, J = 9.7,7.3 = 10.2,4.5Hz, 1 H), 2.26(m, 2 HI, 1.50( 6 , 3 HI, 1.37(9, 3 HI, Hz, 1 H), 3.45(dd, J = 9.7,4.9Hz, 1 H),2.51(ddd, J = 12.2, 1.31(s,3H), 1.30(s,3H);13CNMR6 138.1,128.4, 127.7,127.6, 7.1,7.1Hz, 1 H), 2.11(ddd, J = 12.2,12.2,9.0H~, 1 HI, 1.9-1.2 11.9,107.7,105.1,81.5,80.8, 79.9,76.4,73.2,72.5,72.1,67.2, (m, 10 H); NMR6138.0, 128.3,127.8, 127.7,100.9,78.3,75.2, 37.9,26.8,26.2,25.5,24.8;MS (CVNH3) for C24H370~IN[M + 74.4,73.4,37.8,33.3,31.0,25.7,23.8,23.6,20.0;HRMS NH4]+ 594.1. (CUNH3) calcd for ClsHzg03IN [M + N&l+ 434.1192,found General Procedure for the Reduction of an Iodotet434.1209. rahydrofuran to a (Di)deoxyribose. A mixture of iodotetIodotetrahydrofuranlob; R = benzyl, R = cyclohexyl: rahydrofuran (0.1mmol) and BusSnH (0.5mL) was stirred for Rf0.58,40% ethyl etherhexanes; 'H NMR 6 7.3-7.2(m, 5 H), 6-12 h. The reaction mixture was filtered through silica (100% 5.08(d, J = 3.9Hz, 1 H), 4.55(m, 2 H),4.29(m, 1 H), 4.01(ddd, hexanes containing 2% EtsN, then with hexanesEt20, 50:50 J = 10.6,8.6,3.9 Hz, 1 H), 3.63(m, 1 H), 3.50(dd, J = 10.3, 3.9 containing 2% E a ) . The filtered material was purified by Hz, 1 H), 3.45 (dd, J = 10.3,4.7Hz, 1 H), 2.46(m, 1 H),2.32 chromatography (mixture of hexanesEtz0 with 2% Et3N as (ddd, J = 12.4,8.6, 3.6Hz, 1 H), 1.8-1.2(m, 10 H); 13C NMR 6 eluent). 138.0,128.4,127.7,127.6, 101.4,76.3, 75.4,73.5,71.9,37.1,33.3, (Di)deoxyribose1Sa: lH NMR 6 7.4-7.25(m, 5 H), 5.27 31.3,25.7,23.8,23.7,20.6;MS (CVNH3) for Cl~H2903IN[M + (s, 1 H), 4.60(d, J = 12.2Hz, 1 H), 4.56(d, J = 12.2Hz, 1 H), NH4]+ 434.1. 4.25(m, 1 H), 3.60-3.52(m, 2 H), 3.47(dd, J = 9.7,4.8Hz, 1 Iodotetrahydrofuranlla; R = benzyl, R = (CHa)&'h: Rf H), 2.0-1.0(m, 14 H);13C NMR 6 128.3,127.7,127.5,101.6, 0.28,20% ethyl etherhexanes; IH NMR 6 7.4-7.2(m, 10 H), 78.7,74.8,74.2,73.3,33.8,32.9,31.8,26.6,25.7,24.5,24.2; 4.86(d, J = 4.0Hz, 1 H),4.53( 6 , 2 H), 4.26(m, 1 H), 3.95(ddd, HRMS (CVNH3) calcd for C18H3003N [M + NH4]+ 308.2226, J=12.1,7.9,4.0Hz,lH),3.67(dt,J=9.7,6.0Hz,1H),3.51 found 308.2222. (dd,J=9.8,7.1Hz,lH),3.43(dd,J=10.0,4.8Hz,lH),3.39 (Di)deoxyribose1Sb lH NMR 6 7.4-7.25(m, 5 HI, 5.33 (m,1H),2.71(t,J=7.7Hz,2H),2.5l(m,lH),2.ll(ddd,J= ( d , J = 4.6Hz,lH),4.60( d , J = 12.2Hz, 1H),4.56( d , J = 12.2 12.2,12.2,9.0Hz, 1 H), 1.85(m, 2 H); 13CNMR 6 141.9,138.0, Hz, 1 H), 4.31(m, 1H), 3.57(m, 1 H), 3.48(m, 2 H), 2.2-1.1(m, 128.5,128.4,128.3,127.7,125.7,102.5,78.5,74.1,73.3,66.8, 14 H); 13C NMR 6 128.3,127.7,127.5,102.1,76.7,74.4,73.3, 37.7,32.2,30.9,19.2;HRMS (CVNH3) calcd for CZIHZSO~IN [M 72.5,33.9,32.2,31.9,26.0,25.7,24.5,24.3;MS (CVNH3) for N&]+ 470.1192,found 470.1185. C18H3003N [M + NH41+ 308.1.
+
Iodotetrahydrofuran llb; R = benzyl, R' = (CHdsPh Rf
0.42,20% ethyl etherhexanes; lH NMR 6 7.4-7.2(m, 10 HI, 4.91(d, J = 3.9Hz, 1 H), 4.53(m, 2 H), 4.27(m, 1 H), 4.02(ddd, J = 10.5,8.6,3.9Hz, 1 H), 3.72(dt, J = 9.7,6.2Hz, 1 H), 3.53.4(m, 3 H), 2.74(t, J = 9.1Hz, 2 H),2.45(m, 1 H), 2.32(ddd, J = 12.4,8.7,3.6Hz, 1 H), 1.90(m, 2 H); 13C NMR 6 141.9, 128.6,128.4,127.7,127.6,125.7,102.9,76.4,73.5,71.9,67.1, 37.2,32.2,31.1, 19.9;MS (CUNH3) calcd for C21H26031 [M + HI+ 470.1. Iodotetrahydrofuran 12a; R = thexyldimethylsilyl,R = cyclohexyl: Rf0.38,10% ethyl etherhexanes; IH NMR 6 4.98(d, J = 4.1Hz, 1 H), 4.06(m, 1 H), 3.94(ddd, J = 11.7,7.8, 4.0Hz, 1 H), 3.71(dd, J = 9.9,6.2Hz, 1 H), 3.59(m, 1 H), 3.49 (dd, J = 9.9,6.6Hz, 1 H), 2.49(ddd, J = 12.3,7.2,7.2Hz, 1 H), 2.09(m, 1 H), 1.9-1.2(m, 11 H), 0.85(d, J = 7.0Hz, 6 H), 0.81 ( 8 , 6 H), 0.73/0.68 (d, 6 H); 13C NMR 6 100.7,79.9,75.1,67.3, 38.3,34.2,33.4,31.0,25.8,23.8,23.6,20.4,20.3,18.5,-3.4; HRMS (CVNH3) calcd for ClgH4103INSi [M + NH41+ 486.1901, found 486.1909. Iodotetrahydrofuran 12b; R = thexyldimethylsilyl, R = cyclohexyl: Rf0.48,10%ethyl etherhexane; 'H NMR 6 5.00 (d, J = 3.9Hz, 1 H), 4.13(m, 1H), 3.98(ddd, J = 10.5,8.6, 3.9 Hz,1 H), 3.56(m, 3 H),2.45-2.30(m, 3 H), 1.9-1.2(m, 11 H), 0.85 (d, J = 7.0Hz, 6 H), 0.81( s , 6 H), 0.73/0.68 (d, 6 H). 13C 75.5,64.7,36.8,34.2,33.4,31.4,25.8,23.9, NMR 6 101.5,77.8, 23.7,21.0,20.3, 18.5,-3.4,-3.6;MS (CVNH3) for C19H4103INSi [M + NH4I' 486.1.
(Proto)desilylationof 14d14b. After reduction of iodines 14a/14b, the isolated product (0.05mmol) was diluted with 2 mL of DMF to which was added B a F (0.06mmol, 1.0M in THF) and CsF (0.31mmol,80% tech.). The reaction was heated to 100 "C for 12 h (followed by TLC), after which it was diluted with Et20 and water and the aqueous phase extracted with Et20 (2x). The organic phases were combined and washed with brine, then dried over anhydrous NaSO4 and the solvent evaporated in uucuo. The crude material was purified by column chromatography (mixture of hexanes/EtzO containing 2% of Et3N) to obtain lSa/lSb,which were chromatographically and spectrally identical to the materials isolated from the deiodinations of 7 d 7b.
Acknowledgment. We warmly thank the Universitywide Task Force on AIDS Research for their financial support. SupplementaryMaterial Available: NOE data for compounds 7a and loa, procedures for the preparation of precursors to compounds 13 and 16, and 'H NMR spectra for all tetrahydrofurans (23 pages). This material is contained in libraries on microfiche, immediately follows this article in the microfilm version of the journal, and can be ordered from the ACS; see any current masthead page for ordering information.
509415591
